Journal of Applied Animal Ethics Research 2 (2020) 216–236 brill.com/jaae Do “Prey Species” Hide Their Pain? Implications for Ethical Care and Use of Laboratory Animals Larry Carbone Independent scholar; 351 Buena Vista Ave #703E, San Francisco, CA 94117, USA [email protected] Abstract Accurate pain evaluation is essential for ethical review of laboratory animal use. Warnings that “prey species hide their pain,” encourage careful accurate pain assess- ment. In this article, I review relevant literature on prey species’ pain manifestation through the lens of the applied ethics of animal welfare oversight. If dogs are the spe- cies whose pain is most reliably diagnosed, I argue that it is not their diet as predator or prey but rather because dogs and humans can develop trusting relationships and because people invest time and effort in canine pain diagnosis. Pain diagnosis for all animals may improve when humans foster a trusting relationship with animals and invest time into multimodal pain evaluations. Where this is not practical, as with large cohorts of laboratory mice, committees must regard with skepticism assurances that animals “appear” pain-free on experiments, requiring thorough literature searches and sophisticated pain assessments during pilot work. Keywords laboratory animal ‒ pain ‒ animal welfare ‒ ethics ‒ animal behavior 1 Introduction As a veterinarian with an interest in laboratory animal pain management, I have read articles and reviewed manuscripts on how to diagnose a mouse in pain. The challenge, some authors warn, is that mice and other “prey species” © LARRY CARBONE, 2020 | doi:10.1163/25889567-bja10001 This is an open access article distributed under the terms of the CC BY 4.0Downloaded license. from Brill.com10/02/2021 06:44:55AM via free access Do “Prey Species” Hide Their Pain? 217 may hide or mask their pain (Dwyer, 2004; Malik & Leach, 2017; Allweller, 2019; McLennan et al., 2019; Mogil, 2019; Turner, Pang & Lofgren, 2019; WIRES Northern Rivers, 2020). You approach the cage, the mouse does her best to look fit and strong, and you wrongly assume she’s not in pain. When this happens, pain scientists record incorrect data, or scientists withhold the analgesic medi- cines that might help the mouse feel better, or the veterinarian tells the re- searcher to continue with their animal experiments, all the while assuring the ethics committee, incorrectly, that the experiments are going well and need no further refinement. In this article, I ask if this claim about prey species’ pain manifestation is true, and what ethical implications for practice should follow from deciding on its truth. It is essential to have the most accurate facts about the animals to aim for the most ethical (animal) cost / (human) benefit balance. It is essential to conduct an ethical reckoning of what to do when the facts about animal suffer- ing are limited and uncertain (Carbone, 2019; Institute for Laboratory Animal Research, 2011). If mice, rabbits, sheep or others truly hide signs of pain from humans they perceive as dangerous predators, there are important implications for prac- tice. Pain biologists must factor this into their measurements of animal pain or shift their studies to “non prey” species, if such exist, that are less deceptive. Veterinarians and animal ethics committees must factor in the likelihood of under-diagnosed animal pain in their protocol reviews and pain management plans. All scientists who work with animals must receive training on pain as- sessment strategies that are not confounded by pain-masking behaviors, if there are any. On the other hand, if prey species are easily diagnosed when painful, or by contrast, if all animals challenge easy pain diagnosis, different ethical norms will follow. Three overlapping communities have a stake in accurate mouse pain diag- nosis in the laboratory. Pain biologists using mice to model human pain need accurate, reproducible analgesiometric methods to quantify pain—often pain that they have induced—and the relief that experimental analgesics they are testing provide. Scientists in other fields may also induce pain, but as an unwanted contingency, a side-effect of the experiments they are performing (Russell & Burch, 1959). They must work with their ethics committee and vet- erinarian to assess the likely severity for the animals of experiments they are planning, to plan for preemptive pain management, and to monitor animal welfare during an experiment. Veterinarians and animal caregivers must also monitor for spontaneous pain separate from what the experiments causes, such as fight wounds, cage injuries, and a variety of illnesses animals may Journal of Applied Animal Ethics Research 2 (2020)Downloaded 216–236 from Brill.com10/02/2021 06:44:55AM via free access 218 Carbone develop as they live and age in the vivarium. All of this is extra challenging if human presence suppresses the pain behaviors they are trying to monitor. Pain biologists have refined methods for performing analgesiometry, i.e., measuring pain in animals, especially rodents (Mogil, 2019). Their tools are effi- cient, quantifiable, reproducible. The data they report may generalize to other species, especially humans. Their goal is to generate data, even at the cost of causing pain in their animals, not to manage their research animals as clinical patients. On the other hand, veterinarians in companion animal practice col- laborate with animal guardians or owners, devoting time and effort to diagnose the individual household animal. Their labor is patient-centered and aimed at developing a successful therapeutic plan to treat current pain and reduce situations that exacerbate it. Both approaches to pain assessment can inform best practices for pain management for animals of all species in laboratory ex- periments and both can be thwarted if some species consciously or reflexively somehow mask their pain. Pain biologists’ practices and needs frequently differ from the others. In many model systems, they will choose one or two pain measurement assays and at most a handful of time points, and conduct their studies when they ex- pect peak pain, whether that is hours after injecting an inflammatory agent or weeks after surgically injuring a nerve. If studying analgesic medications, they will run the test when the drug should be at peak levels. After the tests, most such experiments end with the animals’ immediate euthanasia, obviating concerns for ongoing diagnostics and pain management (Mogil, 2019). For the sake of quality data, they must minimize the confounding effects of animals somehow hiding or masking the pain the scientists needs to measure. Mice are thus better objects of study when the scientist’s presence does not affect the readout of the pain measurement. Contrast this with the needs of mice as the feeling subjects of clinical con- cern. By “clinical” in the laboratory context I mean all of the actions scientists and animal care professionals do to maximize animal health and welfare for the sake of the animal. Pain may be acute, during a painful event like a sur- gery, fight or cage injury; subacute, in the convalescent days following a sur- gery; or chronic as illnesses progress. Whereas pain scientists may succeed with a handful of time point measurements to graph the trajectory of pain or analgesia, welfare is a continuous concern for the animal, even if the hu- mans will only evaluate them periodically. Ironically, scientists with the least specialized training in pain recognition may be the ones conducting experi- ments with the highest severity. Their animals are the most in need of accurate and sensitive pain diagnostics. If scientists, veterinarians or caregivers scare Journal of Applied Animal Ethics ResearchDownloaded from2 (2020) Brill.com10/02/2021 216–236 06:44:55AM via free access Do “Prey Species” Hide Their Pain? 219 the animals into hiding their pain, the animals and sometimes the data will suffer (Peterson, Nunamaker & Turner, 2017; Carbone, 2019). My concern here is with a particular subset of painful states, those that are severe enough to affect the animals’ subjective well-being in ways that might benefit from anal- gesics, but not so overwhelming that even a casual observer would know that something is wrong. I appreciate the warning that mouse pain can be hard to detect with an ob- server present. I’ve known scientists and even veterinarians who assume they can quickly look at a cage of five identical white mice, asleep or awake, and know if one of them is painful. When they miss seeing that their mice are in pain during the course of an experiment, they then propagate a cycle, asking their ethics committee to approve further experiments and writing up their scientific reports without ever knowing, and therefore, their audience ever knowing, that the animals on a particular experiment are in fact quite painful and could benefit from analgesics, from refined procedures, or from not doing the procedure at all (Carbone & Austin, 2016). They also miss seeing under- treated pain as a potential source of data confound (Peterson, Nunamaker & Turner, 2017). The idea that rodents as prey animals actively hide their pain is widespread in veterinary, animal welfare, and pain biology literature. But is it true, and are there animals who differ in this regard? Writing with a dual concern for animal welfare and for the predictive value of rodent pain models for human pain biology, Mogil has noted that the idea of prey animals masking their pain seemed a reasonable hypothesis, but could find “no actual data demonstrat- ing differential willingness to display overt pain-related behaviors in prey ver- sus predator species” (Mogil, 2019). I too have challenged authors making this claim to provide a reference to relevant primary data; invariably manuscripts come back with the prey species statement removed rather than supported by citation of data. Scientists, veterinarians and ethics committees need solid information on mouse pain, and on pain in all the animals in laboratories.